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Inhibition of hippocampal OLMα2 cells rescue nicotine induced memory impairment
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Kullander: Formation and Function of Neuronal Circuits.
Brain institute, Federal University of Rio Grande do Norte, Natal - Brazil. (Computational Neurophysiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Kullander: Formation and Function of Neuronal Circuits.
Brain institute, Federal University of Rio Grande do Norte, Natal - Brazil. (Computational Neurophysiology)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Nicotine is a commonly used drug that has been extensively studied for decades. Some of these studies have found cognitive enhancing effects; however, they were usually based on moderate and not the higher doses to which the regular consumer might be accustomed. Here we investigate how higher doses of nicotine may influence the performance of mice in object recognition and in the Y-maze. Further, we examined specific circuits underlying the hippocampal-dependent effects by targeting a subgroup of inhibitory interneurons, referred to as OLMα2 cells. We subjected mice to nicotine during an object recognition task and a working memory task. We found that a high dose of 1.5 mg/kg nicotine impaired memory performance in the object recognition task but not in the working memory task. It was previously demonstrated that OLMα2 cells bidirectionally affect learning in the object recognition task and that these cells respond to nicotine. Subsequently, we subjected mice to nicotine while optogenetically inhibiting OLMα2 cells and found that this intervention reversed the nicotine-induced memory impairment. We conclude that some learning and memory effects from nicotine are hippocampus dependent and are probably mediated by OLMα2 cells.

National Category
Neurosciences
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-439657OAI: oai:DiVA.org:uu-439657DiVA, id: diva2:1542878
Available from: 2021-04-08 Created: 2021-04-08 Last updated: 2021-04-08
In thesis
1. Hippocampal circuit dynamics in learning and value processing of sensory cues: A study into the function of hippocampal microcircuits involving OLMα2 cells
Open this publication in new window or tab >>Hippocampal circuit dynamics in learning and value processing of sensory cues: A study into the function of hippocampal microcircuits involving OLMα2 cells
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The anatomical signatures of the mnemonic/emotional processes share many brain structures, one of which seems to constitute a bridge, the hippocampus. It functions as a structure that consolidates engrams. It is connected to the prefrontal cortex, nucleus accumbens and amygdala, structures that provide emotional salience. This is, from an evolutionary perspective, likely a selection of fitness relevant engrams. Inputs from such structures to the hippocampus increase the likelihood of engram consolidation and behavioral response into long-term deposits. The hippocampal input pathways appear to be of importance for encoding and retrieval processes. During first encounters, entorhinal temporoammonic inputs are necessary for identifying probable threats and encoding of environmental cues. We find that artificial silencing of gate keeper neurons, named oriens lacunosum-moleculare (OLM) cells, increases approach and memory recall of novel cues in several tasks. Further, silencing of OLM cells mediates effective learning by increasing promiscuity in pyramidal cells in response to incoming sensory and/or emotional value inputs from other limbic structures, such as the basolateral amygdala. Depending on the dorsoventral position of the OLM cells, different phenotypes can be observed in different tasks. This is likely, at least in part, because of dorso-ventral differences in the connections between the hippocampus and other structures. In addition, OLM cells can control the specific oscillation frequency theta II (6-8 Hz), which appears in the ventral hippocampus and facilitates approach to predator odors. In conclusion, we show that the hippocampal circuit involving a subtype of OLM cells, is processing value of sensory cues through the temporoammonic pathway, and possibly affecting the basolateral amygdala inputs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2021. p. 49
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1743
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-439659 (URN)978-91-513-1188-3 (ISBN)
Public defence
2021-06-01, On Zoom, Uppsala, 14:00 (English)
Opponent
Supervisors
Available from: 2021-05-07 Created: 2021-04-08 Last updated: 2021-05-25

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Siwani, SamerKullander, Klas

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Kullander: Formation and Function of Neuronal CircuitsScience for Life Laboratory, SciLifeLabDepartment of Medical Cell Biology
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